Fibrinogen Baltimore IV: congenital dysfibrinogenemia with a gamma 275 (Arg----Cys) substitution

The major functional characteristics of fibrinogen Baltimore IV include delayed fibrin monomer polymerization which is not corrected by the addition of calcium, inhibition of normal plasma coagulation upon mixing, and a biphasic polymerization profile in which the abnormal fibrin monomers appear to polymerize at about 2% of the normal rate (Ebert & Bell, Thromb. Res. 38:121-128, 1985). We now report the detection of an abnormal peptide in a comparative peptide map from a cyanogen bromide digest of fibrinogen Baltimore IV. The sequence of this peptide corresponds to the fibrinogen sequence gamma 265-310, except that Arg275 is replaced by Cys. Amino acid analyses of carboxymethylated peptides from control vs. fibrinogen Baltimore IV confirmed the sequencing data. Both the propositus and his affected daughter were heterozygous for the trait.